Abstract
Regulatory T cells (Tregs) are engaged in maintaining immune homeostasis and preventing autoimmunity. Treg cells include thymic Treg cells and peripheral Treg cells, both of which can suppress the immune response via multiple distinct mechanisms. The differentiation, proliferation, suppressive function and survival of Treg cells are affected by distinct energy metabolic programs. Tissue-resident Treg cells hold unique features in comparison with the lymphoid organ Treg cells. Foxp3 transcription factor is a lineage master regulator for Treg cell development and suppressive activity. Accumulating evidence indicates that the activity of Foxp3 protein is modulated by various post-translational modifications (PTMs), including phosphorylation, O-GlcNAcylation, acetylation, ubiquitylation and methylation. These modifications affect multiple aspects of Foxp3 function. In this review, we define features of Treg cells and roles of Foxp3 in Treg biology, and summarize current research in PTMs of Foxp3 protein involved in modulating Treg function. This review also attempts to define Foxp3 dimer modifications relevant to mediating Foxp3 activity and Treg suppression. Understanding Foxp3 protein features and modulation mechanisms may help in the design of rational therapies for immune diseases and cancer.
Highlights
Reviewed by: Jochen Huehn, Helmholtz Center for Infection Research, Germany Zhaocai Zhou, Shanghai Institutes for Biological Sciences (CAS), China
Accumulating evidence indicates that the activity of Foxp3 protein is modulated by various post-translational modifications (PTMs), including phosphorylation, O-GlcNAcylation, acetylation, ubiquitylation and methylation
Tregs are divided into CD44low CD62Lhigh central Tregs and CD44highCD62Llow effector Tregs. cTregs are quiescent, IL-2 signaling dependent and long-lived, and they function in the secondary lymphoid tissues to suppress T cell priming; in contrast, eTregs are highly activated and ICOS signaling dependent with potent suppressive function in specific non-lymphoid tissues to dampen immune responses [12]. eTregs have increased mTORC1 signaling and glycolysis compared with cTregs
Summary
Reviewed by: Jochen Huehn, Helmholtz Center for Infection Research, Germany Zhaocai Zhou, Shanghai Institutes for Biological Sciences (CAS), China. Foxp3 transcription factor is a lineage master regulator for Treg cell development and suppressive activity. Accumulating evidence indicates that the activity of Foxp3 protein is modulated by various post-translational modifications (PTMs), including phosphorylation, O-GlcNAcylation, acetylation, ubiquitylation and methylation.
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